The method(s) of targeting liposomes to specific cell types will be explored both in vitro and in vivo. The first step is to form a stable conjugate between the targeting protein and the liposome surface. This can be accomplished through covalent attachment of a lipid moity to a protein molecule to make it amphipathic and to generate a stable association with the liposomal surface membrane. As a model system, alpha-bungarotoxin will be derivatized with fatty acids or phospholipids. The interactions of liposomes targeted with the derivatized alpha-bungarotoxin and chick myotubes which contain the acetylcholine receptor will be studied. Several parameters such as liposome structure and conditions of presentation to cells will be varied to optimize the specific uptake and transfer of liposome contents to the cells. Basic information from the above studies will be applied to the problem of antibody targeting of liposomes. Purified antibody to the major murine leukemia virus surface glycoprotein, gp70, will be used to target vesicles to leukemia and sarcoma cells bearing this protein antigen. The availability of immunosorbant purified antibody and sensitive radioimmunoassay of gp70 allow an accurate appraisal of the usefulness of this targeting system. Of particular interest is whether attachment of a targeted vesicle to the cell is cooperatively enhanced by multivalent attachment sites through multiple antigen-antibody bonds. Finally, an alveolar cell carcinoma system will be used to study antibody targeted vesicle interaction with mouse model system, typical of human cancer. Studies on the interaction of vesicles to metastesizing cells as well as primary tumors will be conducted.